Preparation of dihydroxanthopterin and xanthopterin



Patented Mar. 16;, 1948 TENT OF PREPARATION OF DIHYDROXANTHOPTERIN ANDXANTHOPTERIN George H. Hitchings, Tuckahoe, N. Y., assignor to BurroughsWellcome & 00. (U. S. A.) Inc., New York, N. Y., a corporation of NewYork No Drawing. Application December 1, 1943,

Serial No. 512,479

3 Claims. 1

rimidine, to form dihydroxanthopterin which with an excess ofchloroacetic acid and purifying to obtain 5-chloroacetamino-2,4-diamino-S-hydroxypyrimidine This product is heated with an aqueous solutionselected from the group consisting of aqueous sodium bicarbonate,disodium phosphate and sodium carbonate to induce ring closure and toform dihydroxanthopterin However, with the stronger alkalies such assodium carbonate and sodium hydroxide, considerable amounts ofimpurities are formed, and

2 it is preferred to effect the ring closure with sodium bicarbonate.The dihydroxanthopterin may be converted to xanthopterin f? I [I HzN-O o/CH by catalytic oxidation in known manner.

The invention is illustrated by the following example:

4 gm. of 2,4,5-triamino-G-hydroxypyrimidine were ground with 12 gm.chloroacetic acid. The mixture was heated in a closed vessel, in which aslight vacuum was maintained, to C. for 15 minutes. The mixture wasextracted with benzene and washed with benzene and ether. The residuewas recrystallized from ml. of 0.2 molar acetate buffer at pH 5.0 togive 5.6 gm. (83% of the theoretical) of 5-chloroacetamino2,4-diamino-B-hydroxypyrimidine.

4.73 gm. of the purified product and 2.88 gm. sodium bicarbonate weredissolved in 100 ml. of boiling water and heated for 2%; hours on aboilin water bath. 15 ml. of normal acetic acid solution were added andthe crystalline material was filtered ofi and dried. This weighed 2.26gm. (62.5% of the theoretical quantity) and a further quantity wasdeposited in the filtrate on standing.

1.17 gm. dihydroxanthopterin were recrystallized from 300 ml. of glacialacetic acid with 200 mg. decolorizing carbon. 1.08 gm. of pure compoundwere obtained.

The purified dihydroxanthopterin was converted into xanthopterin bycatalytic oxidation in the known manner.

What is claimed is:

1. The process of preparing dihydroxanthopterin comprising the steps ofheating 5-chloroacetamino 2,4 diamino 6- hydroxypyrimidine with excesssodium bicarbonate, and recovering dihydroxanthopterin.

2. The process of preparing dihydroxanthopterin comprising the steps ofheating 5-choloroacetamino 2,4 diamino 6 hydroxypyrimidine with anaqueous sodium bicarbonate solution and recovering dihydroxanthopterin.

3. The process of preparing dihydroxanthop- FOREIGN PATENTS terincomprising the steps of heating5-ch1oroacetamino-2,4-diamino-6-hydroxypyrimidine in Number Country Datea boiling water bath with an aqueous sodium 131- 206,454 Germany 1907carbonate solution and recovering dihydroxan- 5 ,7 Germany Feb. 27, 1908the terin.

p GEORGE H. HITCHINGS. OTHER REFERENCES REFERENCES CITED Chem.Abstracts, vol. 35, pages 2147-48.

The following references are of record in the 10 file of this patent:

